Heidi L. Miracle-McMahill

Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States

This study examines the relationship between fatal breast cancer and use of estrogen replacement therapy (ERT) among women in a large prospective study in the United States. After nine years of follow-up, 1,469 breast cancer deaths were observedin a cohort of 422,373 postmenopausal women who were cancer free at study entry and who supplied information on estrogen use. Results from Cox proportional hazards modeling, adjusted for 11 other potential risk factors, showed that ever-use of ERT was associated with a significantly decreased risk of fatal breast cancer (rate ratio [RR]=0.84,95 percent confidence interval [CI]=0.75–0.94). There was a moderate trend (P=0.07) of decreasing risk with younger age at first use of ERT. This decreased risk was most pronounced in women who experienced natural menopause before the age of 40 years (RR=0.59, CI=0.40–0.87). There was no discernible trend of increasing risk with duration of use in estrogen users at baseline or former users, nor was there any trend in years since last use in former users. The relationship between ERT and breast cancer mortality differed by age at menarche and by a self-reported history of breast cysts. No increased risk of fatal breast cancer with ERT was observed with estrogen use status (baseline/former), age at first use, duration of use, or years since last use. These findings suggest that ever-use of ERT is associated with a 16 percent decreased risk of fatal breast cancer.

Family history and risk of fatal prostate cancer.

To examine the relation between fatal prostate cancer and family history of prostate cancer in a first‐degree relative, we analyzed data from a prospective mortality study of 481,011 men with no history of cancer at enrollment in 1982. During 9 years of follow‐up, 1,922 deaths from prostate cancer occurred. Results from Cox proportional hazard models showed that family history of prostate cancer was related to fatal prostate cancer [rate ratio (RR) = 1.60; 95% confidence interval (CI) = 1.31–1.97]; men with two or more affected relatives had a greater than threefold increase in risk (RR = 3.19; 95% CI = 1.51–6.71). Men whose relatives were diagnosed with prostate cancer before age 65 years (RR = 2.03; 95% CI = 1.33–3.09) had a greater effect of family history than men whose relatives were diagnosed at older ages (RR = 1.50; 95% CI = 1.17–1.91). Rate ratios did not increase with decreasing age of the study participants. The 60% increase in risk for men with at least one affected relative is lower than that reported in previous studies.

Family history of breast cancer as a predictor for fatal prostate cancer.

To examine the relation between family history of breast cancer in a mother or sister and a mans risk of fatal prostate cancer, we analyzed data from a prospective mortality study of adult men in the United States. During 12 years of follow-up, there were 3,141 deaths from prostate cancer in a cohort of 480,802 men who were cancer-free at study entry in 1982. Results from Cox proportional hazards models, adjusted for other risk factors, showed a modest increased risk of fatal prostate cancer associated with a family history of breast cancer(in the absence of a family history of prostate cancer) [rate ratio (RR) = 1.16; 95% confidence interval (CI) = 1.01–1.33]. The association was stronger among men younger than 65 years of age whose relatives were diagnosed with breast cancer before age 50 years (RR = 1.65; 95% CI = 0.88–3.10) and among Jewish men (RR = 1.73; 95% CI = 1.00–2.97). The increased risks observed in these subgroups may reflect genetic alterations underlying familial clustering of prostate and breast cancer. (Epidemiology 1998;9:525–529)